Embryonic expression of murine 5T4 oncofoetal antigen is associated with morphogenetic events at implantation and in developing epithelia

Barrow, Katie M.; Ward, Christopher M.; Rutter, Jennifer; Ali, Sumia; Stern, Peter L.

doi:10.1002/dvdy.20482

Cited by 41 publications

(43 citation statements)

References 39 publications

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“…Low levels of 5T4 antigen were detected in the cytoplasm of E-cadherin-positive cells (Fig. 1B, iii), similar to that reported for mouse ES cells (42,44). Furthermore, determination of 5T4 (green) and OCT-4 (red) proteins in spontaneously differentiating HES4 ES cells showed that 5T4 expression correlated with loss of OCT-4 (Fig.…”

Section: Emt Events During Human Es Cell Differentiationsupporting

confidence: 85%

Epithelial-Mesenchymal Transition Events during Human Embryonic Stem Cell Differentiation

et al. 2007

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Epithelial-mesenchymal transition (EMT) occurs during embryonic development and may also be associated with the metastatic spread of epithelial tumors. During EMT, E-cadherin is down-regulated and this correlates with increased motility and invasion of cells. We show that differentiation of human embryonic stem (ES) cells in monolayer culture is associated with an E-to N-cadherin switch, increased vimentin expression, up-regulation of E-cadherin repressor molecules (Snail and Slug proteins), and increased gelatinase (matrix metalloproteinases; MMP-2 and MMP-9) activity and cellular motility, all characteristic EMT events. The 5T4 oncofetal antigen, previously shown to be associated with early human ES cell differentiation, is also part of this process. Abrogation of E-cadherin-mediated cellcell contact in undifferentiated ES cells using neutralizing antibody (nAb) SHE78.7 resulted in increased cellular motility, altered actin cytoskeleton arrangement and a mesenchymal phenotype together with presentation of the 5T4 antigen at the cell surface. nAb-treated ES cells remained in an undifferentiated state, as assessed by OCT-4 protein expression, and did not express EMT-associated transcripts. Removal of nAb from ES cells resulted in the restoration of cell-cell contact, absence of cell surface 5T4, decreased mesenchymal cellular morphology and motility, and enabled the differentiation of the cells to the three germ layers upon their removal from the fibroblast feeder layer. We conclude that E-cadherin functions in human ES cells to stabilize the cortical actin cyoskeletal arrangement and this prevents cell surface localization of the 5T4 antigen. Furthermore, human ES cells represent a useful model system with which to study EMT events relevant to embryonic development and tumor cell metastasis. [Cancer Res 2007;67(23):11254-62]

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Section: Emt Events During Human Es Cell Differentiationsupporting

confidence: 85%

Epithelial-Mesenchymal Transition Events during Human Embryonic Stem Cell Differentiation

et al. 2007

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“…We found that 5T4 expression was associated with high tumorigenic capacity and the undifferentiated state; these results parallel the expression of 5T4 in cycling progenitor cells during embryonic development (18). The association of 5T4 expression with EMT in tumors, observed in the 87426A1 serum-free culture and the 37622A1 PDX, mirrors the association of 5T4 with EMT in normal development (15).…”

Section: T4 and The Cellular Hierarchy In Nsclcsupporting

confidence: 69%

Delineation of a Cellular Hierarchy in Lung Cancer Reveals an Oncofetal Antigen Expressed on Tumor-Initiating Cells

et al. 2011

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Poorly differentiated tumors in non-small cell lung cancer (NSCLC) have been associated with shorter patient survival and shorter time to recurrence following treatment. Here, we integrate multiple experimental models with clinicopathologic analysis of patient tumors to delineate a cellular hierarchy in NSCLC. We show that the oncofetal protein 5T4 is expressed on tumor-initiating cells and associated with worse clinical outcome in NSCLC. Coexpression of 5T4 and factors involved in the epithelial-to-mesenchymal transition were observed in undifferentiated but not in differentiated tumor cells. Despite heterogeneous expression of 5T4 in NSCLC patient-derived xenografts, treatment with an anti-5T4 antibody-drug conjugate resulted in complete and sustained tumor regression. Thus, the aggressive growth of heterogeneous solid tumors can be blocked by therapeutic agents that target a subpopulation of cells near the top of the cellular hierarchy. Cancer Res; 71(12); 4236-46. Ó2011 AACR.

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“…For example, CD9, alkaline phosphatase, stage-specific embryonic antigen (SSEA)-1 and Forssman antigen (FA) are well-known molecules that characterize murine ES cells [18][19][20][21][22]. Among these molecules, SSEA-1 and FA are classified as glycolipid antigens.…”

Section: Discussionmentioning

confidence: 99%

Distribution of Molecular Epitope for Ts4, an Anti-Sperm Auto-Monoclonal Antibody in the Fertilization Process

Shirai

Yoshitake

Maruyama

et al. 2009

Journal of Reproduction and Development

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Abstract. To investigate molecular effects of anti-sperm autoantibodies on fertilization, we previously established antimouse sperm-head auto-monoclonal antibodies (mAbs). Among the mAbs established, one mAb (named Ts4) recognized the sugar moiety of TEX101, a germ cell-marker glycoprotein. In the present study, we examined the immunoreactivity of Ts4 in mouse spermatozoa and fertilized eggs during early embryogenesis to clarify the distribution of the Ts4-reactive antigen in the fertilization process. Similar to TES101 mAb (a specific probe for TEX101), immunopositive staining of Ts4 was observed on spermatocytes, spermatids and spermatozoa within the testis. In contrast to the results obtained with TES101 mAb, Ts4 reacted with the sperm acrosomal region within the cauda epididymis. A Western blot analysis of epididymal sperm extract revealed that Ts4 mainly detected two bands between 100 and 150 kDa, while Ts4 faintly detected a band corresponding to TEX101 at 38 kDa. In addition, Ts4-reactive molecules were observed in the growing early embryo after fertilization. Since Ts4-reactive antigen, potentially a carbohydrate chain, is only observed in reproduction-related areas such as the testis, epididymal sperm-head and early embryo, it is expected to have an effect on fertilization. Therefore, additional studies of this antigen may elucidate the molecular mechanisms underlying the reproductive process. nti-sperm autoantibodies are present in the sera of some infertile patients [1]; however, the precise mechanism underlying the induction of anti-sperm antibodies remains unclear. One leading hypothesis suggests that cross-reactive immune responses against external antigens (e.g., bacterial or viral infections) may induce an immune response against sperm antigens [2]. Based on this hypothesis, we developed several anti-sperm auto-monoclonal antibodies (mAbs) using spleen cells from aged mice (over 1 year old) kept under normal conditions. To identify hybridoma cell lines that secrete anti-sperm autoantibodies, culture media from each hybridoma line were screened for antibody activity against mouse epididymal spermatozoa using ELISA and immunofluorescence tests (Fig.1). To pinpoint the specific antigens recognized by the anti-sperm auto-mAbs, we performed a micro amino acid analysis against testicular proteins that showed an immunopositive reaction for the mAbs using a two-dimensional SDS-PAGE system (Fig.1). Among the mAbs produced, one specific mAb (named Ts4) reacted with a protein that possessed an N-terminus of TYC-QVSQTLSLEDD [3]; this sequence shares 100% sequence identity with the potential N-terminal sequence of TEX10126-39 [4]. TEX101, a highly N-glycosylated glycosylphosphatidylinositol (GPI)-anchored glycoprotein [5], was originally identified as a protein containing the antigen epitope for a specific mAb, called TES101, produced by immunizing female mice with an allogenic testicular homogenate [4]. Previous studies by our research group have demonstrated that TEX101 is a unique germ cell marker that is ...

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Embryonic expression of murine 5T4 oncofoetal antigen is associated with morphogenetic events at implantation and in developing epithelia

Cited by 41 publications

References 39 publications

Epithelial-Mesenchymal Transition Events during Human Embryonic Stem Cell Differentiation

Epithelial-Mesenchymal Transition Events during Human Embryonic Stem Cell Differentiation

Delineation of a Cellular Hierarchy in Lung Cancer Reveals an Oncofetal Antigen Expressed on Tumor-Initiating Cells

Distribution of Molecular Epitope for Ts4, an Anti-Sperm Auto-Monoclonal Antibody in the Fertilization Process

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